Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.

Objective : To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients. Methods: Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. Results: MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one. Conclusions Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.

Objective To investigate the interventional effect and mechanism of a novel ampelopsis hydrogel on dampness-heat accumulation syndrome of gouty arthritis. Methods A total of 90 patients with gouty arthritis who met the diagnostic criteria of western medicine and were differentiated as damp-heat accumulation syndrome of traditional Chinese medicine(TCM) were randomly divided into treatment group, control group and blank group, with 30 patients in each group. The blank group was treated with etoricoxib only, the control group was treated with etoricoxib combined with ampelopsis hydrogel, and the treatment group was treated with etoricoxib combined with external application of ampelopsis hydrogel. The clinical efficacy, time to symptom improvement, safety, comfort, changes in syndrome scores of TCM, serum inflammatory factors[C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), erythrocyte sedimentation rate (ESR)], NF-κB signaling pathway-related proteins, Visual Analogue Scale (VAS) scores for pain, and joint mobility were compared among the three groups before and after treatment. Results The total effective rates in the treatment group and control group were 93.33% and 90.00%, respectively, which were higher than 70.00% in the blank group (P < 0.05). The time for improvement of pain, redness, tenderness, and limited joint mobility in the treatment group was shorter than that in the control group and blank group (P < 0.05). After 7 days of treatment, the TCM syndrome score in the treatment group was lower than that in the control group and blank group, and the levels of serum CRP, TNF-α, and ESR and the expressions of NF-κB signalingpathway-related proteins P50 and P65 in the treatment group and control group were lower than those in the blank group (P < 0.05). After 7 days of treatment, the VAS score in the treatment group was lower than that in the control group and blank group, and the comfort score in the treatment group was higher than that in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions among the three groups (P>0.05). Conclusion The effect of ampelopsis hydrogel in treating gouty arthritis is better than that of ampelopsis paste, and its mechanism may be related to the regulation of the NF-κB pathway and inhibition of inflammatory factor expression. The hydrogel is easy to use, hygienic, and comfortable, and is expected to become a safe, effective, and convenient external medicine for gouty arthritis.

Objective To evaluate and summarize the evidence related to the prevention of parenteral nutritional support complications in inpatients,and to provide an evidence-based basis for guiding healthcare professionals to prevent parenteral nutritional support complications in a scientific and standardized manner.Methods Computerized search was conducted in UpToDate,BMJ Best Clinical Practice,Centre for Evidence-Based Health Care database of the Joanna Briggs Institute in Australia,Ontario Registered Nurses Association website in Canada,National Institute for Health and Clinical Excellence website in the United Kingdom,Scottish Intercollegiate Guidelines Network,Guidelines International,New Zealand Guidelines Collaborative,American Society for Parenteral and Enteral Nutrition website,European Society for Clinical Nutrition and Metabolism Society website,International Practice Guidelines Registry Platform China Clinical Guidelines Repository,Medical Pulse,PubMed,Cochrane Library,Web of Science,CINAHL,Embase,China Biomedical Literature Database,CNKI,Wanfang Database,etc.The search period was from the time of database construction to October 2023.After literature screening and quality evaluation,the evidence extraction and integration were carried out.Results A total of 16 papers were included,including 3 clinical decision-making,1 evidence summary,4 guidelines,6 expert consensuses,and 2 systematic evaluations.27 pieces of best evidence were extracted from 3 areas,namely metabolic complications,mechanical complications,and infectious complications.Conclusion This study summarized the evidence related to the prevention and management of complications of parenteral nutrition support in adult inpatients,aiming to provide an evidence-based basis for healthcare professionals to develop scientific and standardized measures for the prevention and management of complications of parenteral nutrition support.

Objective To construct a nomogram risk prediction model for symptomatic cerebrovas-cular ischaemia based on intra-plaque neovascularisation in carotid arteries in patients with ische-mic cerebrovascular disease(ICVD).Methods A retrospective study was conducted on 320 ICVD patients who were consecutively admitted to Wuhan Fourth Hospital from April 2020 to April 2024.In a ratio of 3∶1,240 cases were assigned into a training set and 80 cases into a validation set.The patients in the training set were further divided into 147 cases in the symptomatic sub-group and 93 cases in the asymptomatic subgroup according to the presence or absence of relevant symptoms or signs.Multifactorial logistic regression analysis was used to identify the risk factors for symptomatic ischemia in ICVD patients,and a nomogram risk prediction model was construc-ted and the prediction efficacy of the model was evaluated.Results The proportions of plaque multiplicity,ulcerated plaque,stenosis ≥70％,and intra-plaque neovascularization were signifi-cantly higher in the symptomatic subgroup than the asymptomatic subgroup(P＜0.05,P＜0.01).Multifactorial logistic regression analysis showed that plaque multiplicity(OR=1.261,95％CI:1.088-1.539,P=0.003),ulcerated plaque(OR=1.458,95％CI:1.132-1.661,P=0.001),and stenosis ≥70％(OR=2.023,95％CI:1.458-2.561,P=0.001),and intra-plaque neovasculariza-tion(OR=1.206,95％CI:1.057-1.489,P=0.002)were independent risk factors for the occur-rence of symptomatic cerebral ischemia in ICVD patients.H-L deviation test showed that the con-structed nomogram risk prediction model had a good fit(x2=9.362,P=0.295).Internal and ex-ternal validation showed that the calibration curves for both the training and validation sets were consistent with the original curves,and the AUC value was were 0.871 and 0.864,respectively.De-cision curve analysis showed that the model had a significant standardized clinical net benefit when the predicted risk threshold exceeded 0.01.Conclusion Ultrasonography is instructive in as-sessment of the presence or absence of intra-plaque neovascularization in carotid atherosclerotic plaques.And our constructed nomogram risk prediction model has good predictive value for the development of symptomatic cerebral ischemia.

Objective:To study the value of coronary flow reserve (CFR) via dynamic single photon emission computed tomography (D-SPECT) in evaluating coronary microcirculation dysfunction (CMD) in patients with heart failure.Methods:A prospective research method was adopted. One hundred and ninety-four patients with heart failure from September 2019 to September 2020 in Zhongshan Hospital, Fudan University were selected. The patients were tested for CFR using D-SPECT, and CFR<2 was defined as CMD. The general data were recorded, including age, gender, body mass index (BMI), blood pressure, heart rate, smoking history, New York Heart Association (NYHA) heart function classification, comorbidities and medication situation. The laboratory test results were recorded, including blood urea nitrogen, blood creatinine, blood uric acid, estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hs-CRP), cardiac troponin T (cTnT) and N terminal pro B type natriuretic peptide (NT-proBNP). The left atrial diameter (LAD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal thickness (IVST), pulmonary artery systolic pressure (PASP) and left ventricular ejection fraction (LVEF) were measured by cardiac ultrasound. After discharge, patients were followed up in outpatient or telephone contact, with the primary endpoint event being a composite endpoint consisting of cardiovascular death and heart failure readmission. Multiple linear regression analysis was used to analyze the risk factors of CFR. The Kaplan-Meier survival curve was draw, and the log-rank test was used to evaluate the effect of CFR on prognosis.Results:Among 194 patients, 133 patients had CMD (CMD group), and the incidence of CMD was 68.56%; 61 patients did not have CMD (non-CMD group). There were no statistical differences in gender composition, BMI, smoking history proportion, blood pressure, heart rate, hypertension rate, atrial fibrillation rate, diabetes mellitus rate, renal dysfunction rate, medication situation, LAD, LVEDD, IVST, PASP, blood urea nitrogen, blood creatinine, blood uric acid, eGFR and hs-CRP between two groups ( P>0.05). The age, rate of NYHA heart function classification Ⅲ to Ⅳ grade, rate of myocardial infarction or revascularization history, LVESD, cTnT and NT-proBNP in CMD group were significantly higher than those in non-CMD group: (60.7 ± 14.0) years old vs. (55.9 ± 15.8) years old, 54.89% (73/133) vs. 26.23% (16/61), 22.56% (30/133) vs. 1.64% (1/61), (48.8 ± 13.1) mm vs. (44.6 ± 11.4) mm, 0.023 (0.015, 0.046) μg/L vs. 0.015 (0.010, 0.023) μg/L and 1 591 (751, 3 409) ng/L vs. 1 132 (288, 1 860) ng/L, the LVEF was significantly lower than that in non-CMD group: (40.9 ± 14.2)% vs. (45.5 ± 14.1)%, and there were statistical differences ( P<0.05 or <0.01). Multiple linear regression analysis result showed that the cTnT was an risk factor of CFR ( β = - 0.18, 95% CI - 0.82 to - 0.06, P = 0.025). The median followed up time was 230 (136 to 330) d, 10 patients were lost to follow-up, with 58 patients in CMD group completing follow-up and 126 patients in the non-CMD group. The incidences of primary endpoint event and heart failure readmission in CMD group were significantly higher than those in non-CMD group: 23.02% (29/126) vs. 3.45% (2/58) and 15.87% (20/126) vs. 3.45% (2/58), and there were statistical differences ( P<0.01); there was no statistical difference in incidence of cardiovascular death between two groups ( P>0.05). Kaplan-Meier survival curve analysis result showed that the event free survival rate in CMD group was significantly lower than that in non-CMD group, and there was statistical difference (log-rank χ2 = 11.92, P<0.01). Conclusions:CMD is highly prevalent in patients with heart failure, and it is associated with poor prognosis. Improving CMD for improving coronary microcirculation may be potential targets for the treatment of heart failure.

Objective:To investigate the effectiveness of case-based learning (CBL) combined with online teaching in standardized residency training of rheumatology and immunology.Methods:A total of 78 individuals who participated in standardized residency training in Department of Rheumatology and Immunology in our hospital from June 2019 to August 2020 were included and divided into observation group and control group. The individuals in the control group received traditional teaching, and those in the observation group received CBL combined with online teaching. The physicians receiving standardized residency training were evaluated by theoretical examination, clinical operation skill assessment, and instructor rating, and the degree of satisfaction with teaching, degree of satisfaction with teaching methods, and classroom learning atmosphere were also evaluated.Results:The observation group had a theoretical examination score of (94.10±2.01) and a clinical operation skill assessment score of (90.44±1.57), which were significantly higher than those of the control group ( P<0.05), and the observation group had a significantly better instructor rating (89.36±1.33) than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher degree of satisfaction with teaching (3.79±0.41), degree of satisfaction with teaching methods (3.92±0.27), and evaluation of classroom learning atmosphere (3.90±0.31) ( P<0.05). Conclusion:CBL combined with online teaching can help to improve learning efficiency, stimulate the enthusiasm for learning, expand clinical thinking, promote the growth of teaching and learning, and form a virtuous cycle among trainees receiving standardized residency training, which holds promise for further exploration.

Background: and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

Objective:To investigate the correlation between thyroid tumor volume ratio to lymph node metastasis in papillary thyroid carcinoma (PTC).Methods:The ratio of thyroid tumors volume to resected thyroid volume was measured by imaging methods before surgery, and the correlation between volume ratio and other clinicopathological features and lymph node metastasis in 134 patients with single focal PTC was analyzed.Results:The number of lymph node metastases was associated with age <45 years and invasion of the capsule ( r<0.300, P<0.05), and weakly correlated with gender, maximum tumor diameter, tumor volume and volume ratio. Among them, the correlation between patho-volume ratio was strongest ( r=0.379, P<0.001). Male genter was an independent risk factor for central cervical lymph node metastasis (χ 2=13.597 P<0.05). The co-predictions of sex and volume ratio was AUC=0.760, sensitivity=0.574 and specificity=0.818. Conclusion:Compared to the maximum diameter of tumors, the volume ratio in papillary thyroid carcinoma better predicts the metastasis of lymph nodes of papillary thyroid carcinoma in the central region.